Lysophosphatidylserine lipase ABHD12

Definition

Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes. Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal. Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways. Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding.

References:

[1]. Daisuke Ogasawara, et al. Selective blockade of the lyso-PS lipase ABHD12 stimulates immune responses in vivo. Nat Chem Biol. 2018 Dec;14(12):1099-1108. [Content Brief]

[2]. Dhanashree S Kelkar, et al. A chemical-genetic screen identifies ABHD12 as an oxidized-phosphatidylserine lipase. Nat Chem Biol. 2019 Feb;15(2):169-178. [Content Brief]

[3]. Dong-Hui Chen, et al. Two novel mutations in ABHD12: expansion of the mutation spectrum in PHARC and assessment of their functional effects. Hum Mutat. 2013 Dec;34(12):1672-8. [Content Brief]

[4]. Juha R Savinainen, et al. Biochemical and pharmacological characterization of the human lymphocyte antigen B-associated transcript 5 (BAT5/ABHD16A). PLoS One. 2014 Oct 7;9(10):e109869. [Content Brief]

[5]. Dina Navia-Paldanius, et al. Biochemical and pharmacological characterization of human α/β-hydrolase domain containing 6 (ABHD6) and 12 (ABHD12). J Lipid Res. 2012 Nov;53(11):2413-24. [Content Brief]

[6]. Alaumy Joshi, et al. Biochemical characterization of the PHARC-associated serine hydrolase ABHD12 reveals its preference for very-long-chain lipids. J Biol Chem. 2018 Nov 2;293(44):16953-16963. [Content Brief]

[7]. Daisuke Ogasawara, et al. Discovery and Optimization of Selective and in Vivo Active Inhibitors of the Lysophosphatidylserine Lipase α/β-Hydrolase Domain-Containing 12 (ABHD12). J Med Chem. 2019 Feb 14;62(3):1643-1656. [Content Brief]

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